【摘要】：目的研究二甲雙胍對小鼠骨關(guān)節(jié)炎及軟骨細(xì)胞分化的影響。方法切除小鼠右膝關(guān)節(jié)的內(nèi)側(cè)半月板和前交叉韌帶造模骨關(guān)節(jié)炎,造模成功后,隨機(jī)分為2組,實驗組給予二甲雙胍(2mg/kg/d)而對照組予等量的生理鹽水灌胃干預(yù)治療8周,通過HE、番紅O-快速綠切片染色和Micro-CT觀察關(guān)節(jié)結(jié)構(gòu)變化,進(jìn)行Mankin評分評估關(guān)節(jié)炎嚴(yán)重程度,通過Western Blot檢測各組關(guān)節(jié)軟骨AMPK、mTOR的活性及自噬程度;取新生小鼠肋軟骨和膝關(guān)節(jié)軟骨進(jìn)行細(xì)胞培養(yǎng),隨機(jī)分為實驗組(2mmol/L的二甲雙胍)和空白對照組,觀察軟骨細(xì)胞形態(tài)、數(shù)量,MTT法檢測細(xì)胞活性,Western Blot檢測軟骨細(xì)胞AMPK、mTOR的活性及自噬程度。結(jié)果 (1)成功構(gòu)建了小鼠骨關(guān)節(jié)炎模型,HE、番紅O-快速綠染色、MicroCT結(jié)果及Mankin評分證明二甲雙胍能保護(hù)骨關(guān)節(jié)炎;(2)關(guān)節(jié)軟骨Western Blot結(jié)果顯示二甲雙胍能激活A(yù)MPK,增強(qiáng)自噬保護(hù)骨關(guān)節(jié)炎;(3)MTT法顯示二甲雙胍抑制軟骨細(xì)胞增殖分化,Western Blot結(jié)果顯示二甲雙胍促進(jìn)軟骨細(xì)胞自噬。結(jié)論二甲雙胍通過激活A(yù)MPK信號通路,抑制mTOR信號通路,促進(jìn)軟骨細(xì)胞自噬,發(fā)揮保護(hù)骨關(guān)節(jié)炎作用。
[Abstract]:Objective to study the effect of metformin on osteoarthritis and chondrocyte differentiation in mice. Methods the medial meniscus and anterior cruciate ligament (ACL) were excised from the right knee joint of mice. After successful modeling, the mice were randomly divided into two groups. The experimental group was treated with metformin (2mg/kg/d) and the control group was treated with the same amount of normal saline for 8 weeks. The changes of articular structure were observed by Micro-CT, and the severity of arthritis was evaluated by Mankin score. The activity of AMPK mTOR and the degree of autophagy of articular cartilage were detected by Western Blot. The chondrocytes were cultured in the costal cartilage and knee cartilage of newborn mice and were randomly divided into two groups: the experimental group (metformin of 2mmol/L) and the blank control group. The morphology of chondrocytes was observed. The activity of AMPK mTOR and the degree of autophagy in chondrocytes were detected by quantitative MTT assay and Western Blot. Results (1) A mouse model of osteoarthritis was successfully constructed. The results of MicroCT and Mankin score showed that metformin could protect osteoarthritis, and (2) Western Blot of articular cartilage showed that metformin could activate AMPK and enhance autophagy. (3) MTT assay showed that metformin inhibited the proliferation and differentiation of chondrocytes. Western Blot showed that metformin promoted autophagy of chondrocytes. Conclusion Metformin activates AMPK signaling pathway, inhibits mTOR signaling pathway, promotes chondrocyte autophagy and protects osteoarthritis.
【作者單位】： 廣州醫(yī)科大學(xué)附屬第三醫(yī)院荔灣醫(yī)院;深圳市福田區(qū)第二人民醫(yī)院;南方醫(yī)科大學(xué)第三附屬醫(yī)院創(chuàng)傷骨科;中山大學(xué)附屬第八醫(yī)院(深圳福田)骨科;
【基金】：深圳市福田區(qū)衛(wèi)生公益性科研項目(Ftws2017011)
【分類號】：R684.3

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